L0301P68 - Neural Communication and Integration
Synaptic Transmission *most common mechanism in neuron-to-neuron communication *between two neurons: **very close 20-50nm gap (synaptic cleft) **pre-synaptic neuron ***vesicles of pre-synthesised NT **post-synaptic neurons involved ***receptors lined up in synaptic area, ready to respond to NT when released **one-to-one interaction   Systems Simple EPSP System *a single EPSP rarely ever generates a postsynaptic AP **1 EPSP does not necessarily equal 1 AP **allows for control and regulation: ***flexibility - not every stimulus will definitely create a response ***plasticity - the response changes s circumstances change *only 6/10 EPSPs create a post-synaptic AP **most decay to below the threshold by the time it reaches the axon hillock *overcome by two types of summation  Temporal Summation *piggybacking APs **second EPSP occurs on top of the first *a single presynaptic neuron fires many times in succession *cumulative effect on the post-synaptic membrane causes it to fire an AP Spatial Summation *multiple presynaptic cells firing simultaneously - different areas of input on the same cell *adding on to each other and creating an AP (if the timing is correct) Simple IPSP System *IPSP makes a post-synaptic neuron less likely to generate an action potential *NT binding causes hyperpolarisation by: **net influx of negative ions (Cl-) **net efflux of positive ions (K+) *reduced chance for AP generation as threshold is not reached *increases membrane leakiness = diminishing action potential *either deliberate within the body, or caused by drugs (anaesthetics) Combination of EPSPs and IPSPs *also known as postsynaptic inhibition *EPSP and IPSP occurs at the same time, by the time the depolarisation current reaches the axon hillock, if the sum is: **above threshold = AP generated **below threshold = no AP generated Presynaptic Inhibition *axo-axonal inhibition *GABAa receptors allow influx of Cl- causing very minor hyperpolarisation *membrane becomes more leaky such that AP decays and does not activate NT release Importance of Inhibitory Synapses *absence = mayhem **neurons are too easily excitable *on soma **inhibits all inputs into that cell *on presynaptic axon **restriction to particular inputs Facilitation *successive EPSPs are larger than the first *this is due to residual calcium in bouton Summary Diagrams Modulation of Transmitter Release Two methods: *presynaptic receptors (facilitation) *metabotropic receptors (numbers) Metabotropic Receptors *possess 7 transmembrane segments *not an ion channel but does react with NTs *generally located away from the synapse *takes longer than ionotropic receptors, but can be open for a longer period of time *can have widespread effects in other parts of the cell through secondary messengers and is not restricted to the synaptic area   *widely utilised by neurotransmitters **dopamine, noradrenaline **serotonin **glutamate (mGluR) **GABA (GABAb) **acetylcholine (mACh) ***fast response in ionotropic receptors ***very slow response in MR Activation of MR *lower concentrations of transmitter likely involved in activation *results in: **interaction between receptor and G-proteins (on inside of plasma membrane) **leads to a second messenger transduction process Presynaptic MR *decrease probability of release of NT *a pathway that is used often will often operate quicker than one that is rarely used Postsynaptic MR *slow down the synaptic response *may be no change in membrane potential G-Proteins *possess 3 parts **α - binds to activated receptor and activates various second messenger cascades inducing a cellular response **β and γ - partly embedded in plasma membrane to prevent G-protein from moving away Neurotransmission Diseases Acetylcholine nicotinic receptor *Alzheimer’s disease *Nocturnal epilepsy *Myasthenia gravis **receptors on skeletal muscle Glycine inhibitory receptor/channel *Absence epilepsy *Startle disease **spinal cord to skeletal muscle 'Glutamate NMDA receptor ' *Stroke **too much Ca2+ causes cell death Central Neurotransmitters *Glutamate **ionotropic NMDA and AMPA receptors **metabotropic receptors **affected in many neurological diseases *Acetylcholine **excitatory ionotropic nicotinic receptors **metabotropic muscarinic receptors *Catecholamines: dopamine, noradrenaline **metabotropic receptors **affected in Parkinson’s disease and addictions *Serotonin **metabotropic receptors **affected in depression  Drugs *does not give you more/less receptors *just changes stimulation/inhibition of the receptors Alcohol *acute alcohol - inhibits EPSP *in the absence of alcohol when one is alcohol dependent - increased release of GABA Morphine *acts on metabotropic receptors *reduces influx of Ca2+ and hence less transmitter release *suppresses G-proteins: **cAMP **VGCCs (reserve pool) *also activates opening of K channels **postsynaptic membrane becomes hyperpolarised - no AP created Cocaine *reduces dopamine reuptake for release *lots of dopamine left in the synaptic cleft and overstimulates neurons Methamphetamine *similar in structure to dopamine *is taken up in reuptake into the neuron causing damage to dopamine neurons *leaves dopamine in the synapse to overstimulate neurons as well *widespread effects on mood *motor function severely impaired Plasticity *modulation of synaptic strength depends on: **longterm potentiation (LTP) OR **longterm depression (LTD) Probability of Release *chances of a docked vesicle fusing with PM and releasing transmitter when AP invades **0 (never releases)-1 (releases everytime) *can be influenced by “use” of the synapse Use of Synapse *increases probability of release by: **increase size of synapse ***pre-synaptic: increased number of release sites per bouton ***post-synaptic: density of receptor/channels *occurs due to release and actions of brain derived neurotropic factor (BDNF) *forms the basis of LTP Longterm Potentiation *larger EPSP following period of high-frequency stimulation *required for memory formation *experiment to show this: **single pulse applied every 20s **tetanic stimulation (4 episodes of 100Hz stimulation for 1s) applied **single pulse every 20s resumed for 2hr **EPSPs were larger than before   Longterm Depression *EPSPs will be reduced *occurs in dementia Astrocytes *glial cell in the brain that support neurons by regulating the surrounding ionic and chemical environment *means that neurons do not have to waste ATP to reuptake used NTs *more numerous than neurons *effectiveness decreases with age